Membrane Transport Processes in the Eye

The present work relates the turbidity of the eye to microscopic spatial fluctuations in its index of refraction. Such fluctuations are indicated in electron microscope photographs. By examining the superposition of phases of waves scattered from each point in the medium, we provide a mathematical demonstration of the Bragg reflection principle which we have recently used in the interpretation of experimental investigations: namely, that the scattering of light is produced only by those fluctuations whose fourier components have a wavelength equal to or larger than one half the wavelength of light in the medium. This consideration is applied first to the scattering of light from collagen fibers in the normal cornea. We demonstrate physically and quantitatively that a limited correlation in the position of near neighbor collagen fibers leads to corneal transparency. Next, the theory is extended to predict the turbidity of swollen, pathologic corneas, wherein the normal distribution of collagen fibers is disturbed by the presence of numerous lakes-regions where collagen is absent. A quantitative expression for the turbidity of the swollen cornea is given in terms of the size and density of such lakes. Finally, the theory is applied to the case of the cataractous lens. We assume that the cataracts are produced by aggregation of the normal lens proteins into an albuminoid fraction and provide a formula for the lens turbidity in terms of the molecular weight and index of refraction of the individual albuminoid macromolecules. We provide a crude estimate of the mean albuminoid molecular weight required for lens opacity.

The objective of this study was to collect a comprehensive database of ocular tissue permeability measurements found in a review of the literature to guide models for drug transport in the eye. Well over 300 permeability measurements of cornea, sclera, and conjunctiva, as well as corneal epithelium, stroma, and endothelium, were obtained for almost 150 different compounds from more than 40 different studies. In agreement with previous work, the corneal epithelium was shown generally to control transcorneal transport, where corneal stroma and endothelium contribute significantly only to the barrier for small, lipophilic compounds. In addition, other quantitative comparisons between ocular tissues are presented. This study provides an extensive database of ocular tissue permeabilities, which should be useful for future development and validation of models to predict rates of drug delivery to the eye.

Molecular biology entered the field of mammalian amino acid transporters in 1990-1991 with the cloning of the first GABA and cationic amino acid transporters. Since then, cDNA have been isolated for more than 20 mammalian amino acid transporters. All of them belong to four protein families. Here we describe the tissue expression, transport characteristics, structure-function relationship, and the putative physiological roles of these transporters. Wherever possible, the ascription of these transporters to known amino acid transport systems is suggested. Significant contributions have been made to the molecular biology of amino acid transport in mammals in the last 3 years, such as the construction of knockouts for the CAT-1 cationic amino acid transporter and the EAAT2 and EAAT3 glutamate transporters, as well as a growing number of studies aimed to elucidate the structure-function relationship of the amino acid transporter. In addition, the first gene (rBAT) responsible for an inherited disease of amino acid transport (cystinuria) has been identified. Identifying the molecular structure of amino acid transport systems of high physiological relevance (e.g., system A, L, N, and x(c)- and of the genes responsible for other aminoacidurias as well as revealing the key molecular mechanisms of the amino acid transporters are the main challenges of the future in this field.